TY - JOUR
T1 - Increased vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) expression in adolescent brain development
T2 - A longitudinal micro-PET/CT study in rodent
AU - Jiang, Donglang
AU - Lu, Xiuhong
AU - Li, Zijing
AU - Rydberg, Nicklas
AU - Zuo, Chuantao
AU - Peng, Fangyu
AU - Hua, Fengchun
AU - Guan, Yihui
AU - Xie, Fang
N1 - Funding Information:
This research project was supported by the National Science Foundation of China (81571345), National Key Research and Development Program Foundation of China (2016YFC1306403), Natural Science Foundation and Major Basic Research Program of Shanghai (16JC1420502), program of the Shanghai Science and Technology Commission (17511107103 and 17411953500), and Fudan University-SIBET Medical Engineering Joint Fund (yg2017-003) to YG. This research was also sponsored by the Shanghai Sailing Program (18YF1403200) and startup fund of Huashan Hospital, Fudan University (2017QD081) to FX.
Publisher Copyright:
© 2019 Jiang, Lu, Li, Rydberg, Zuo, Peng, Hua, Guan and Xie.
PY - 2019
Y1 - 2019
N2 - Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18 F-PF-(+)-DTBZ, 11 C-CFT, and 18 F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Results: Variable uptake of 18 F-PF-(+)-DTBZ and 11 C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18 F-PF-(+)-DTBZ and 11 C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18 F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Conclusion: Age-dependent increases of striatal of 18 F-FDG, 18 F-PF-(+)-DTBZ, and 11 C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.
AB - Background: Brain development and maturation in adolescence is a complex process with active changes of metabolic and neurotransmission pathways. Positron emission tomography (PET) is a useful imaging modality for tracking metabolic and functional changes in adolescent brain. In this study, changes of glucose metabolism, expression of vesicular monoamine transporter 2 and dopamine transporter during adolescent brain development in rats were investigated with PET/CT. Methods: A longitudinal PET/CT study of age-dependent changes of VMAT2, DAT and glucose metabolism in adolescent brain was conducted in a group of Wistar rats (n = 6) post sequential intravenous injection of 18 F-PF-(+)-DTBZ, 11 C-CFT, and 18 F-FDG, respectively. PET acquisition was performed at 2, 4, 9, and 12 months of age. Radiotracer uptake in different brain regions, including the striatum, cerebellum, and hippocampus, were quantified and recorded as Standardized uptake value (SUV) and striatal specific uptake ratio (SUVR: SUV in brain regions/SUV in cerebellum). Results: Variable uptake of 18 F-PF-(+)-DTBZ and 11 C-CFT were detected, with highest level uptake in the striatum and accumbens. There was significant age-dependent increase of 18 F-PF-(+)-DTBZ and 11 C-CFT uptake in the striatum from 2 months of age (SUV: 1.36 ± 0.22, 1.37 ± 0.39, respectively), to 4 months (SUV: 2.22 ± 0.29, 2.04 ± 0.33), 9 months (1.98 ± 0.34, 2.09 ± 0.18), 12 months (SUV: 1.93 ± 0.19, 2.00 ± 0.17) of age, SUV of 18 F-FDG also increased from 2 months of age to older ages (SUV in the striatum: 3.71 ± 0.78 at 2 month, 5.28 ± 0.81, 5.14 ± 0.73, 4.94 ± 0.50 at 4, 9, 12 month, respectively). Conclusion: Age-dependent increases of striatal of 18 F-FDG, 18 F-PF-(+)-DTBZ, and 11 C-CFT uptake were detected in rats from 2 to 4 month of age, demonstrating striatal development presents over the first 4 months of age. Four months of age can be considered a safe threshold to launch brain disease studies for exclusion of confusion of continuing tissue development. These findings support further investigation of age-dependent changes in expression of DAT, VMAT2, and glucose metabolism for their potential use as a new imaging biomarker for study of brain development and functional maturation.
KW - Brain development
KW - Dopamine transporter (DAT)
KW - Glucose metabolism
KW - Positron emission tomography
KW - Vesicular monoamine transporter 2 (VMAT2)
UR - http://www.scopus.com/inward/record.url?scp=85061961699&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061961699&partnerID=8YFLogxK
U2 - 10.3389/fnins.2018.01052
DO - 10.3389/fnins.2018.01052
M3 - Article
C2 - 30697146
AN - SCOPUS:85061961699
SN - 1662-4548
VL - 12
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
M1 - 1052
ER -